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Resveratrol inhibits Trypanosoma cruzi arginine kinase and exerts a trypanocidal activity.
- Source :
-
International journal of biological macromolecules [Int J Biol Macromol] 2016 Jun; Vol. 87, pp. 498-503. Date of Electronic Publication: 2016 Mar 11. - Publication Year :
- 2016
-
Abstract
- Arginine kinase catalyzes the reversible transphosphorylation between ADP and phosphoarginine which plays a critical role in the maintenance of cellular energy homeostasis. Arginine kinase from the protozoan parasite Trypanosoma cruzi, the etiologic agent of Chagas disease, meets the requirements to be considered as a potential therapeutic target for rational drug design including being absent in its mammalian hosts. In this study a group of polyphenolic compounds was evaluated as potential inhibitors of arginine kinase using molecular docking techniques. Among the analyzed compounds with the lowest free binding energy to the arginine kinase active site (<-6.96kcal/mol), resveratrol was chosen for subsequent assays. Resveratrol inhibits 50% of recombinant arginine kinase activity at 325μM. The trypanocidal effect of resveratrol was evaluated on the T. cruzi trypomastigotes bursting from infected CHO K1 cells, with IC50=77μM. Additionally epimastigotes overexpressing arginine kinase were 5 times more resistant to resveratrol compared to controls. Taking into account that: (1) resveratrol is considered as completely nontoxic; (2) is easily accessible due to its low market price; and (3) has as a well-defined target enzyme which is absent in the mammalian host, it is a promising compound as a trypanocidal drug for Chagas disease.<br /> (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Subjects :
- Drug Design
Enzyme Inhibitors metabolism
Molecular Docking Simulation
Polyphenols pharmacology
Protein Conformation
Resveratrol
Stilbenes metabolism
Trypanocidal Agents metabolism
Trypanosoma cruzi drug effects
Arginine Kinase antagonists & inhibitors
Enzyme Inhibitors pharmacology
Stilbenes pharmacology
Trypanocidal Agents pharmacology
Trypanosoma cruzi enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0003
- Volume :
- 87
- Database :
- MEDLINE
- Journal :
- International journal of biological macromolecules
- Publication Type :
- Academic Journal
- Accession number :
- 26976067
- Full Text :
- https://doi.org/10.1016/j.ijbiomac.2016.03.014